• The Journal of Internal Korean Medicine
• /
• v.29 no.3
• /
• pp.657-665
• /
• 2008

Objectives : The objective of this study was to assess the effect of acupuncture applied at the ST36 point on blood pressure and endothelial dependent vasodilation in hypertensive patients. Methods : 24 hypertensive patients were recruited and randomized to a study group (12 subjects) or a control group (12 subjects). Both groups took FMD (endothelial-dependant, flow-mediated dilation) measurement and then acupuncture needles were inserted at ST36 for the study group. In the control group, they took sham acupuncture as a control. FMD was rechecked after 10-min acupuncture treatment. Blood pressure was measured before and after acupuncture treatment. Results : FMD increased significantly in the study group after acupuncture (9.5${\pm}$2.0% to 11.1${\pm}$2.2%), but not in the control group. In both groups, there were no changes in blood pressure and heart rate. Conclusions : Acupuncture on ST36 appears to improve endothelial dysfunction of hypertensive patients and this might result from inducing activation of endothelium-derived nitric oxide.

• BMB Reports
• /
• v.43 no.9
• /
• pp.584-592
• /
• 2010

Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in the pathogenesis of cardiovascular and neurodegenerative diseases, which develop under oxidative stress conditions. It appears that a balanced interplay between BH4 and NOS is crucial for cellular fate. If cellular BH4 homeostasis maintained by BH4 synthesis and regeneration fails to cope with increased oxidative stress, NOS is uncoupled to generate superoxide rather than NO and, in turn, exacerbates impaired BH4 homeostasis, thereby leading to cell death. The fundamental biochemical events involved in the BH4-NOS interplay are essentially the same, as revealed in mammalian endothelial, cardiac, and neuronal cells. This review summarizes information on the cellular BH4 homeostasis in mammals, focusing on its regulation under normal and oxidative stress conditions.

• Journal of Pharmaceutical Investigation
• /
• v.23 no.1
• /
• pp.1-9
• /
• 1993

The endothelial cell of brain capillary called the blood-brain barrier (BBB) has carrier-mediated transport systems for nutrients and drugs. The mechanism of the BBB transport of basic and acidic drugs has been reviewed and examined for endogenous transport systems in BBB in WKY and SHRSP. Acidic drugs such as salicylic acid and basic drugs such as eperisone are taken up in a carrier mediated manner through the BBB via the monocarboxylic acid and amine transport systems. The specific dysfunction for the choline transport at the BBB in SHRSP would affect the function of the brain endothelial cell and brain parenchymal cell. The utilization of the endogenous transport systems of monocarboxylic acid and amine could be promising strategy for the effective drug delivery to the brain.

• Toxicological Research
• /
• v.30 no.3
• /
• pp.141-148
• /
• 2014

Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin ($PGI_2$), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.

• IMMUNE NETWORK
• /
• v.15 no.4
• /
• pp.206-211
• /
• 2015

Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-${\delta}$ (PKC-${\delta}$) in ALI has been a controversial topic. Here we investigated PKC-${\delta}$ function in ALI using PKC-${\delta}$ knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-${\delta}$ KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-${\delta}$ inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-${\delta}$-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-${\delta}$ inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-${\delta}$ inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.

• BMB Reports
• /
• v.47 no.10
• /
• pp.552-557
• /
• 2014

The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and ${\beta}$-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and ${\beta}$-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase $C{\alpha}$ ($PKC{\alpha}$). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.15 no.3
• /
• pp.123-128
• /
• 2011

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.

• Natural Product Sciences
• /
• v.18 no.4
• /
• pp.266-272
• /
• 2012

Hyperglycemia or high glucose (HG), is the hallmark of diabetes, known to induce oxidative stress, release of chemokines, and cytokines, which confer endothelial cell damage. On the other hand, microbial transformation of organic materials often leads to certain changes in their product structures which could enhance their biological activities. The aim of this study was to investigate the beneficial effects of fermented Gastrodia elata (FGE) in HG induced human umbilical vein endothelial cells (HUVECs) dysfunction. GE, fermented by Saccharomyces cerevisiae, which has an extensive history of safe use, exhibited higher phenolic compounds content than those of Gastrodia elata (GE). The HG-induced production of nitric oxide (NO) and interleukin-8 (IL-8) were significantly attenuated by FGE pretreatment to the cells, in a concentration dependent manner. In addition, FGE showed marked activity in free radical scavenging. These results suggest that FGE possesses beneficial effects in protecting against the oxidative stress, and inflammatory conditions in endothelial cells, caused by HG.

• Journal of Ginseng Research
• /
• v.37 no.4
• /
• pp.413-424
• /
• 2013

Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of human umbilical vein endothelial cells (HUVECs) in a serum-deprived apoptosis model. KRGE protected HUVECs from serum-deprived apoptosis by inhibiting mitochondrial cytochrome c release and caspase-9/-3 activation. This protective effect was significantly higher than that of American ginseng extract. KRGE treatment increased antiapoptotic Bcl-2 and Bcl-$X_L$ protein expression and Akt-dependent Bad phosphorylation. Moreover, KRGE prevented serum deprivation-induced subcellular redistribution of these proteins between the mitochondrion and the cytosol, resulting in suppression of mitochondrial cytochrome c release. In addition, KRGE increased nitric oxide (NO) production via Akt-dependent activation of endothelial NO synthase (eNOS), as well as inhibited caspase-9/-3 activities. These increases were reversed by co-treatment of cells with inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) and pre-incubation of cell lysates in dithiothreitol, indicating KRGE induces NO-mediated caspase modification. Indeed, KRGE inhibited caspase-3 activity via S-nitrosylation. These findings suggest that KRGE prevents serum deprivation-induced HUVEC apoptosis via increased Bcl-2 and Bcl-$X_L$ protein expression, PI3K/Akt-dependent Bad phosphorylation, and eNOS/NO-mediated S-nitrosylation of caspases. The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases.

• Korean Journal of Pharmacognosy
• /
• v.54 no.1
• /
• pp.21-26
• /
• 2023

Cirsium japonicum var. maackii is a traditional Korean wild perennial herb used to treat blood circulation, high blood pressure, inflammation, diabetes, and kidney damage. However, it is not known whether C. japonicum var. maackii directly improves endothelial dysfunction. In this study, the effect of C. japonicum var. maackii (CJE) on tumor necrosis factor (TNF)-α-induced vascular inflammation was investigated in vitro using human umbilical vein endothelial cells (HUVEC). As a result, CJE inhibited the production of VCAM-1, ICAM-1 and ROS increased by TNF-α in HUVECs. In addition, treatment with CJE attenuated IκB phosphorylation and translocation of NF-κB to the nucleus. These results suggest that CJE can suppress TNFα-induced adhesion molecule expression by blocking NF-κB signaling and inhibiting ROS generation. The results of this study show that CJE has the potential to be used to treat and prevent inflammation associated with endothelial cell damage.